Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl- 11C]WAY-100635 independent of arterial sampling

Hahn, Andreas, Nics,Lukas, Baldinger, Pia, Ungersbock, Johanna, Dolliner, Peter, Frey, Richard, Birkfellner, Wolfgang, Mitterhauser, Markus, Wadsak, Wolfgang, Karanikas, Georgios, Kasper, Siegfried and Lanzenberger, Rupert (2012) Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl- 11C]WAY-100635 independent of arterial sampling. NeuroImage, 62 1: 199-206. doi:10.1016/j.neuroimage.2012.04.047

Author Hahn, Andreas
Baldinger, Pia
Ungersbock, Johanna
Dolliner, Peter
Frey, Richard
Birkfellner, Wolfgang
Mitterhauser, Markus
Wadsak, Wolfgang
Karanikas, Georgios
Kasper, Siegfried
Lanzenberger, Rupert
Title Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl- 11C]WAY-100635 independent of arterial sampling
Journal name NeuroImage   Check publisher's open access policy
ISSN 1053-8119
Publication date 2012-08-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.neuroimage.2012.04.047
Open Access Status Not yet assessed
Volume 62
Issue 1
Start page 199
End page 206
Total pages 8
Place of publication Amsterdam, The Netherlands
Publisher Elsevier BV
Language eng
Subject 2805 Cognitive Neuroscience
2808 Neurology
Abstract Image-derived input functions (IDIFs) represent a promising technique for a simpler and less invasive quantification of PET studies as compared to arterial cannulation. However, a number of limitations complicate the routine use of IDIFs in clinical research protocols and the full substitution of manual arterial samples by venous ones has hardly been evaluated. This study aims for a direct validation of IDIFs and venous data for the quantification of serotonin-1A receptor binding (5-HT 1A) with [carbonyl- 11C]WAY-100635 before and after hormone treatment. Methods: Fifteen PET measurements with arterial and venous blood sampling were obtained from 10 healthy women, 8 scans before and 7 after eight weeks of hormone replacement therapy. Image-derived input functions were derived automatically from cerebral blood vessels, corrected for partial volume effects and combined with venous manual samples from 10min onward (IDIF+VIF). Corrections for plasma/whole-blood ratio and metabolites were done separately with arterial and venous samples. 5-HT 1A receptor quantification was achieved with arterial input functions (AIF) and IDIF+VIF using a two-tissue compartment model. Results: Comparison between arterial and venous manual blood samples yielded excellent reproducibility. Variability (VAR) was less than 10% for whole-blood activity (p>0.4) and below 2% for plasma to whole-blood ratios (p>0.4). Variability was slightly higher for parent fractions (VARmax=24% at 5min, p<0.05 and VAR<13% after 20min, p>0.1) but still within previously reported values. IDIFs after partial volume correction had peak values comparable to AIFs (mean difference δ=-7.6±16.9kBq/ml, p>0.1), whereas AIFs exhibited a delay (δ=4±6.4s, p<0.05) and higher peak width (δ=15.9±5.2s, p<0.001). Linear regression analysis showed strong agreement for 5-HT 1A binding as obtained with AIF and IDIF+VIF at baseline (R 2=0.95), after treatment (R 2=0.93) and when pooling all scans (R 2=0.93), with slopes and intercepts in the range of 0.97 to 1.07 and -0.05 to 0.16, respectively. In addition to the region of interest analysis, the approach yielded virtually identical results for voxel-wise quantification as compared to the AIF. Conclusions: Despite the fast metabolism of the radioligand, manual arterial blood samples can be substituted by venous ones for parent fractions and plasma to whole-blood ratios. Moreover, the combination of image-derived and venous input functions provides a reliable quantification of 5-HT 1A receptors. This holds true for 5-HT 1A binding estimates before and after treatment for both regions of interest-based and voxel-wise modeling. Taken together, the approach provides less invasive receptor quantification by full independence of arterial cannulation. This offers great potential for the routine use in clinical research protocols and encourages further investigation for other radioligands with different kinetic characteristics.
Keyword Arterial input function
Image derived input function
Kinetic analysis
Serotonin 1A
Venous blood
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
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